HSV type 1 genome variants from persistently productive infections in Raji and BJAB cell lines

We studied possible genomic changes occurring in herpes simplex virus type 1 (HSV-1) during long-term cell culture which served as a model system for persistence and latency studies as introduced earlier. Sixteen HSV-1 reisolates were isolated from persistently productive HSV-1 (strains F and AK)-infected Burkitt lymphoma cell lines Raji and BJAB at four different times. They were roughly characterized in plaque morphology, plaque size, and infectivity. The viral reisolate DNAs revealed deletions and insertions of up to 1,150 base pairs in fragments BamHI-B, -E, -F, -J, -V, -X, and in the L-terminal and junction fragments S and K. Results were confirmed by additional restriction enzyme analyses and DNA sequencing of selected genomic regions between map units 0.642-0.650, 0.763-0.778 and 0.887-0.934. There was a progressive increase in genomic variability over a three-year period. However, changes in DNA fragment size occurred at different rates, with some reisolates showing stability over several months. The selective pressure for HSV-1 (F and AK) genomic changes was stronger in Raji than in BJAB cells, and stronger for F than for AK strain.